[The paradigm of abnormal sensory gating in fear extinction as pathophysiology in obsessive-compulsive disorder]

The processes of fear conditioning and extinction are thought to be related to the pathophysiology of anxiety disorders, including obsessive-compulsive disorder (OCD), panic disorder, and posttraumatic stress disorder. We have reported alterations of auditory P50 suppression in human fear conditioning and extinction in healthy control subjects (Kurayama, et al., 2009). In addition, we have reported that P50 suppression in fear extinction was impaired in patients with OCD (Nanbu, et al., 2010). The present report reviewed the studies about relationship between sensory gating and fear conditioning. In the acquisition phase of classical fear conditioning, 10 pairings of the conditioned stimulus (CS; a visual stimulus from a light-emitting diode) and the unconditioned stimulus (US; an electrical stimulus to the wrist) were administered; in the extinction phase, 10 CS without US were administered. P50 auditory evoked potentials were measured as the first stimulus sound (S1) and the second stimulus sound (S2) in a double-click paradigm with a 500 ms interval (shorter than usual), and P50 S2/S1 ratios were used to evaluate P50 suppression. In healthy controls, the mean P50 S2/S1 ratio in the fear acquisition phase was significantly elevated compared with the ratio found in the control phase, while it recovered to basal level in the extinction phase. The mean P50 S2/S1 ratio in patients with OCD was significantly higher than the ratio in controls (P = 0.022) in the extinction phase, in contrast to the lack of significant difference found in the baseline and acquisition phases. Sensory gating mechanisms may be physiologically associated with fear conditioning, and OCD may involve abnormal sensory gating in fear extinction.